Submissions for variant NM_024577.4(SH3TC2):c.2017G>A (p.Ala673Thr)

gnomAD frequency: 0.00001  dbSNP: rs201985394

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000654184	SCV000776074	likely benign	Charcot-Marie-Tooth disease type 4	2025-01-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001155698	SCV001317148	uncertain significance	Charcot-Marie-Tooth disease type 4C	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001155699	SCV001317149	uncertain significance	Susceptibility to mononeuropathy of the median nerve, mild	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV002422422	SCV002724348	uncertain significance	Inborn genetic diseases	2022-04-06	criteria provided, single submitter	clinical testing	The c.2017G>A (p.A673T) alteration is located in exon 11 (coding exon 11) of the SH3TC2 gene. This alteration results from a G to A substitution at nucleotide position 2017, causing the alanine (A) at amino acid position 673 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV003126893	SCV003803569	uncertain significance	not provided	2023-02-10	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Previously reported as a variant of uncertain significance in an individual with PHARC syndrome who also homozygous for a nonsense variant in another gene associated with this syndrome (Thimm et al., 2020); This variant is associated with the following publications: (PMID: 32077159)
Mayo Clinic Laboratories, Mayo Clinic	RCV003126893	SCV005411895	uncertain significance	not provided	2023-10-17	criteria provided, single submitter	clinical testing	BP4