Submissions for variant NM_001130987.2(DYSF):c.5488C>T (p.Pro1830Ser)

gnomAD frequency: 0.00014  dbSNP: rs145832952

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726065	SCV000341697	uncertain significance	not provided	2016-12-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000726065	SCV000536483	uncertain significance	not provided	2023-08-08	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000560446	SCV000649725	uncertain significance	Qualitative or quantitative defects of dysferlin	2022-10-19	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1791 of the DYSF protein (p.Pro1791Ser). This variant is present in population databases (rs145832952, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. ClinVar contains an entry for this variant (Variation ID: 69635). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DYSF protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl	RCV000666060	SCV000790296	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2017-03-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000560446	SCV001301315	uncertain significance	Qualitative or quantitative defects of dysferlin	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). 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.
Revvity Omics, Revvity	RCV000726065	SCV003829633	uncertain significance	not provided	2024-01-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004019072	SCV004861692	uncertain significance	Inborn genetic diseases	2024-01-04	criteria provided, single submitter	clinical testing	The c.5371C>T (p.P1791S) alteration is located in exon 48 (coding exon 48) of the DYSF gene. This alteration results from a C to T substitution at nucleotide position 5371, causing the proline (P) at amino acid position 1791 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000666060	SCV001463476	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2B	2020-01-17	no assertion criteria provided	clinical testing