Submissions for variant NM_024577.4(SH3TC2):c.3686A>T (p.Asp1229Val)

gnomAD frequency: 0.00306  dbSNP: rs146920285

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082893	SCV000218575	likely benign	Charcot-Marie-Tooth disease type 4	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000713265	SCV000292687	likely benign	not provided	2020-08-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 21291453, 27884173, 25025039, 27582484, 32376792)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000237055	SCV000297314	uncertain significance	not specified	2015-11-08	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000713265	SCV000339049	uncertain significance	not provided	2016-01-22	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000237055	SCV000843854	benign	not specified	2020-03-10	criteria provided, single submitter	clinical testing
Mendelics	RCV000987610	SCV001136995	benign	Charcot-Marie-Tooth disease type 4C	2019-05-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000713265	SCV001154547	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	SH3TC2: BS1, BS2
Illumina Laboratory Services, Illumina	RCV000987610	SCV001318730	uncertain significance	Charcot-Marie-Tooth disease type 4C	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001157181	SCV001318731	uncertain significance	Susceptibility to mononeuropathy of the median nerve, mild	2018-02-13	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV000789576	SCV001335908	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000237055	SCV001433771	likely benign	not specified	2018-02-22	criteria provided, single submitter	clinical testing	The c.3686A>T; p.Asp1229Val variant (rs146920285) has been reported in the heterozygous state, in the absence of any other detected pathogenic SH3TC2 variants, in two HMSN I patients (Lassuthova 2011) and one CMT2 patient; however, the variant did not segregate with disease in the CMT family (Hoyer 2014). This variant is listed in the genome Aggregation Database (gnomAD) with a non-Finnish European population frequency of 0.4% (identified on 510 out of 126,418 chromosomes), in the Saudi Human Genome Program with a frequency of 2.6% (identified on 102 out of 3,920 chromosomes; Abouelhoda 2016), and is classified as likely benign/uncertain significance in ClinVar (ID: 188089). Based on the available information, the p.Asp1229Val variant is likely to be benign.
Ambry Genetics	RCV002453563	SCV002614252	likely benign	Inborn genetic diseases	2021-06-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Inherited Neuropathy Consortium	RCV000789576	SCV000928932	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only
PreventionGenetics, part of Exact Sciences	RCV004535140	SCV004738370	likely benign	SH3TC2-related disorder	2020-03-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).